Charcot-Marie-Tooth neuropathies: Current gene therapy advances and the route toward translation.
J Peripher Nerv Syst
; 28(2): 150-168, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-36965137
Charcot-Marie-Tooth (CMT) neuropathies are a group of genetically and phenotypically heterogeneous disorders that predominantly affect the peripheral nervous system. Unraveling the genetic and molecular mechanisms, as well as the cellular effects of CMT mutations, has facilitated the development of promising gene therapy approaches. Proposed gene therapy treatments for CMTs include virally or non-virally mediated gene replacement, addition, silencing, modification, and editing of genetic material. For most CMT neuropathies, gene- and disease- and even mutation-specific therapy approaches targeting the neuronal axon or myelinating Schwann cells may be needed, due to the diversity of underlying cellular and molecular-genetic mechanisms. The efficiency of gene therapies to improve the disease phenotype has been tested mostly in vitro and in vivo rodent models that reproduce different molecular and pathological aspects of CMT neuropathies. In the next stage, bigger animal models, in particular non-human primates, provide important insights into the translatability of the proposed administration and dosing, demonstrating scale-up potential and safety. The path toward clinical trials is faced with further challenges but is becoming increasingly feasible owing to the progress and knowledge gained from clinical applications of gene therapies for other neurological disorders, as well as the emergence of sensitive outcome measures and biomarkers in patients with CMT neuropathies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Charcot-Marie-Tooth
Límite:
Animals
Idioma:
En
Revista:
J Peripher Nerv Syst
Asunto de la revista:
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Chipre
Pais de publicación:
Estados Unidos